Cardiac troponin T Arg92Trp mutation and progression from hypertrophic to dilated cardiomyopathy

Citation
N. Fujino et al., Cardiac troponin T Arg92Trp mutation and progression from hypertrophic to dilated cardiomyopathy, CLIN CARD, 24(5), 2001, pp. 397-402
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems
Journal title
CLINICAL CARDIOLOGY
ISSN journal
0160-9289 → ACNP
Volume
24
Issue
5
Year of publication
2001
Pages
397 - 402
Database
ISI
SICI code
0160-9289(200105)24:5<397:CTTAMA>2.0.ZU;2-8
Abstract
Background: Mutations in the cardiac troponin T gene causing familial hyper trophic cardiomyopathy (HCM) are associated with a very poor prognosis but only mild hypertrophy. To date, the serial morphologic changes in patients with HCM linked to cardiac troponin T gene mutations have not been reported . Hypothesis: The aim of this study was to determine the long-term course of patients with familial HCM caused by the cardiac troponin T gene mutation, Arg92Trp. Methods: In all, 140 probands with familial HCM were screened for mutations in the cardiac troponin T gene. Results: The Arg92Trp missense mutation was present in 10 individuals from two unrelated pedigrees. They exhibited different cardiac morphologies: thr ee had dilated cardiomyopathy- like features, five had asymmetric septal hy pertrophy with normal left ventricular systolic function, one had electroca rdiographic abnormalities without hypertrophy, and one had the disease-caus ing mutation but did not fulfill the clinical criteria for the disease. The mean maximum wall thickness was 14.1 +/- 6.0 mm. The three patients with d ilated cardiomyopathy-like features had progressive left ventricular dilati on. Three individuals underwent right ventricular endomyocardial biopsy. Th ere was a modest degree of myocardial hypertrophy (myocyte diameter: 18.9 /- 5.2 mum), and minimal myocardial disarray and mild fibrosis were noted. Conclusion: The Ag92Trp substitution in the cardiac troponin T gene shows a high degree of penetrance, moderate hypertrophy, and early progression to dilated cardiomyopathy in Japanese patients. Early identification of indivi duals with this mutation may provide the opportunity to evaluate the effica cy of early therapeutic interventions.